Clostridium Difficile Infection

“Highly infectious spore-forming and toxin-producing gram positive anaerobic bacillus, which causes an important hospital-acquired infection responsible for 20-30% of antibiotic-associated colitis”

Risk Factors

• Antibiotic use (within the last 2 weeks)
  • Especially fluoroquinolones, clindamycin and broad-spectrum penicillins and cephalosporins.
  • Multiple antibiotics or long duration of antibiotics also increases risk.
• Age ≥65
• Hospitalisation
• Severe underlying comorbidities
• Gastric acid suppression (e.g. PPI medication)
• Enteral feeding GI surgery
• Obesity
• Chemotherapy

Aetiology

• There are toxigenic (exotoxin producing) and non-toxigenic (cannot produce exotoxins) strains of C. difficile.  
• Non-toxigenic strains are found in around 2% of healthy adults as commensals in the bowel.
• Only toxigenic strains cause disease.  
• C. difficile spreads via spores released from asymptomatic or symptomatic carriers of the pathogen.
  • These spores are highly infectious and resistant to acid, heat and antibiotics

Pathophysiology

1. Antibiotics disrupt normal colonic microbiota, which usually compete with C. difficile.
2. Toxigenic strains of C difficile are resistant to antibiotics and are able to multiply and release toxins → pseudomembranous colitis (appearance on endoscopy).
3. Toxins cause colonic inflammation, intestinal fluid secretion, mucosal damage, neutrophil activation

Clinical Presentation

• Watery diarrhoea (≥3 loose bowel motions within 24 hours)
• Abdominal pain
• Nausea & fever.

• Mild:
  • No systemic features,
  • ≤3 bowel motions per day
  • Normal WCC
• Moderate:
  • 3-5 bowel motions
  • Raised WCC
• Severe:
  • WCC > 15×10⁹
  • Raised creatinine
  • Fever >38.5 or evidence of severe colitis.
• Fulminant:
  • Hypotension
  • Tachycardia
  • Ileus (partial or complete)
  • Toxic megacolon
  • CT evidence of severe disease

Investigations

• Bloods:
  • WCC (↑)
  • Routine bloods (FBC, U&Es, LFTs)
  • Blood cultures
  • VBG (lactate)
• Imaging:
  • Abdominal X-ray
  • CT abdomen pelvis (if severe disease)
  • Flexible sigmoidoscopy (usually avoided)
• Special:
  • C. difficile toxin in stool – NAAT (nucleic acid amplification testing
  • EIA (enzyme immunoassay e.g. enzyme glutamate dehydrogenase))
  • C. difficile antigen in stool (only shows exposure, not active infection)

Management

• SIGHT:
  • Suspect
  • Isolate within 2 hours
  • Gloves and aprons
  • Hand washing with soap and water
  • Test immediately.

• Correct fluid losses.
• Stop current antibiotics.
• Mild/moderate:
  • Metronidazole PO for 10-14 days
• Severe:
  • Vancomycin PO for 10-14 days.
  • Switch to fidaxomicin or add metronidazole if no improvement at 7 days.
• Fulminant:
  • Vancomycin PO and metronidazole PO.
  • IV metronidazole if ileus.
• Recurrent CDI:
  • Faecal microbiota transplantation (FMT)

Complications

• Hypotension,
• Ileus
• Toxic megacolon (>6cm)
• Bowel perforation
• Shock